scholarly journals Soybean-Derived Peptides Attenuate Hyperlipidemia by Regulating Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 95
Author(s):  
Haksoo Lee ◽  
Eunguk Shin ◽  
Hyunkoo Kang ◽  
HyeSook Youn ◽  
BuHyun Youn
Keyword(s):  
Bile Acid ◽  
Mouse Models ◽  
Bioactive Peptides ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Peptide Sequence ◽  
Cholesterol Excretion

Increased triglyceride, cholesterol, and low-density lipoprotein (LDL) levels cause hyperlipidemia. Despite the availability of statin-based drugs to reduce LDL levels, additional effective treatments for reducing blood lipid concentrations are required. Herein, soybean hydrolysate prepared via peptic and tryptic hydrolysis promoted trans-intestinal cholesterol excretion (TICE) by increasing ATP-binding cassette subfamily G member 5 (ABCG5) and ABCG8 expression. The peptide sequence capable of promoting TICE was determined via HPLC and LC-MS/MS. Based on this, pure artificial peptides were synthesized, and the efficacy of the selected peptides was verified using cellular and hyperlipidemic mouse models. Soybean hydrolysates, including two bioactive peptides (ALEPDHRVESEGGL and SLVNNDDRDSYRLQSGDAL), promoted TICE via the expression of ABCG5 and ABCG8 in enterocytes. They downregulated expression of hepatic cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1 via expression of fibroblast growth factor 19 (FGF19) in a liver X receptor α (LXRa)-dependent pathway. Administration of bioactive peptides to hyperlipidemic mouse models by oral gavage reduced cholesterol levels in serum via upregulation of ABCG5 and ABCG8 expression in the proximal intestine and through fecal cholesterol excretion, upregulated FGF 15/19 expression, and suppressed hepatic bile acid synthesis. Oral administration of soybean-derived bioactive peptides elicited hypolipidemic effects by increasing TICE and decreasing hepatic cholesterol synthesis.

scholarly journals Growth Hormone Induces Low-Density Lipoprotein Clearance but not Bile Acid Synthesis in Humans

2004 ◽  
Vol 24 (2) ◽  
pp. 349-356 ◽  
Author(s):  
Suzanne Lind ◽  
Mats Rudling ◽  
Sverker Ericsson ◽  
Hans Olivecrona ◽  
Mats Eriksson ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Bile Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Low Density

scholarly journals Hypolipidemic Roles of Casein-Derived Peptides by Regulation of Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3058
Author(s):  
Sungmin Lee ◽  
BuHyun Youn
Keyword(s):  
Bile Acid ◽  
Bioactive Peptides ◽  
Oral Treatment ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
In Vivo Models ◽  
Intestinal Excretion ◽  
Cholesterol Excretion

Hyperlipidemia, a syndrome characterized by an abnormal elevation of blood lipids, causes chronic lethal metabolic disorders. Although statins are regularly prescribed to patients, an alternative to treat the burden of excessive lipids is required for cholesterol control. In this study, it was found that the treatment of casein hydrolyzed by pepsin and trypsin induced trans-intestinal cholesterol excretion (TICE) through ATP-binding cassette subfamily G members 5 (ABCG5) expression. Next, we analyzed sequences of the peptides responsible for TICE induction, synthesized artificial peptides based on the sequences, and the hypolipidemic effects of the peptide treatments were assessed in both in vitro and in vivo models. We determined that two bioactive peptides contained in casein hydrolysates (SQSKVLPVPQK and HPHPHLSF) induced TICE through the expression of ABCG5 in enterocytes and suppressed hepatic mRNA expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1by ileal FGF19 expression both in an liver X receptor α (LXRα)-mediated manner. In the hyperlipidemic mouse models, the oral administration of peptides reduced serum cholesterol levels through elevation of the ABCG5 expression in proximal intestine and fecal cholesterol secretion. Besides this, peptides induced ileal expression of fibroblast growth factor 15/19 (FGF15/19) and inhibited hepatic bile acid synthesis. We found that the oral treatment of casein-derived bioactive peptides could improve hyperlipidemia by regulating intestinal excretion and hepatic synthesis of cholesterols.

scholarly journals Intestine-Specific Overexpression of LDLR Enhances Cholesterol Excretion and Induces Metabolic Changes in Male Mice

Endocrinology ◽  
2018 ◽  
Vol 160 (4) ◽  
pp. 744-758 ◽  
Author(s):  
Luca Meoli ◽  
Danny Ben-Zvi ◽  
Courtney Panciotti ◽  
Stephanie Kvas ◽  
Palmenia Pizarro ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Treatment Options ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Metabolic Effects ◽  
Cholesterol Levels ◽  
Cholesterol Excretion

Abstract Roux-en-Y gastric bypass (RYGB) surgery is one of the most effective treatment options for severe obesity and related comorbidities, including hyperlipidemia, a well-established risk factor of cardiovascular diseases. Elucidating the molecular mechanisms underlying the beneficial effects of RYGB may facilitate development of equally effective, but less invasive, treatments. Recent studies have revealed that RYGB increases low-density lipoprotein receptor (LDLR) expression in the intestine of rodents. Therefore, in this study we first examined the effects of RYGB on intestinal cholesterol metabolism in human patients, and we show that they also exhibit profound changes and increased LDLR expression. We then hypothesized that the upregulation of intestinal LDLR may be sufficient to decrease circulating cholesterol levels. To this end, we generated and studied mice that overexpress human LDLR specifically in the intestine. This perturbation significantly affected intestinal metabolism, augmented fecal cholesterol excretion, and induced a reciprocal suppression of the machinery related to luminal cholesterol absorption and bile acid synthesis. Circulating cholesterol levels were significantly decreased and, remarkably, several other metabolic effects were similar to those observed in RYGB-treated rodents and patients, including improved glucose metabolism. These data highlight the importance of intestinal cholesterol metabolism for the beneficial metabolic effects of RYGB and for the treatment of hyperlipidemia.

Role of AMACR (α-methylacyl-CoA racemase) and MFE-1 (peroxisomal multifunctional enzyme-1) in bile acid synthesis in mice

2014 ◽  
Vol 461 (1) ◽  
pp. 125-135 ◽  
Author(s):  
Kaija J. Autio ◽  
Werner Schmitz ◽  
Remya R. Nair ◽  
Eija M. Selkälä ◽  
Raija T. Sormunen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Mouse Models ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Wild Type ◽  
Multifunctional Enzyme

Bile acid analysis of wild-type, Mfe-1−/−, Amacr−/− and Amacr−/−Mfe-1−/− mouse models shows that peroxisomal multifunctional enzyme 1 can participate in bile acid synthesis in both AMACR-dependent and AMACR-independent pathways.

scholarly journals Myostatin Knockout Regulates Bile Acid Metabolism by Promoting Bile Acid Synthesis in Cattle

Animals ◽  
2022 ◽  
Vol 12 (2) ◽  
pp. 205
Author(s):  
Di Wu ◽  
Mingjuan Gu ◽  
Zhuying Wei ◽  
Chunling Bai ◽  
Guanghua Su ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Negative Regulator ◽  
Bile Acid Metabolism ◽  
Metabolomic Analysis ◽  
Metabolomics Data

Myostatin (MSTN) is a major negative regulator of skeletal muscle mass and causes a variety of metabolic changes. However, the effect of MSTN knockout on bile acid metabolism has rarely been reported. In this study, the physiological and biochemical alterations of serum in MSTN+/− and wild type (WT) cattle were investigated. There were no significant changes in liver and kidney biochemical indexes. However, compared with the WT cattle, lactate dehydrogenase, total bile acid (TBA), cholesterol, and high-density lipoprotein (HDL) in the MSTN+/− cattle were significantly increased, and glucose, low-density lipoprotein (LDL), and triglycerides (TG) were significantly decreased, indicating that MSTN knockout affected glucose and lipid metabolism and total bile acids content. Targeted metabolomic analysis of the bile acids and their derivatives was performed on serum samples and found that bile acids were significantly increased in the MSTN+/− cattle compared with the WT cattle. As the only bile acid synthesis organ in the body, we performed metabolomic analysis on the liver to study the effect of MSTN knockout on hepatic metabolism. Metabolic pathway enrichment analysis of differential metabolites showed significant enrichment of the primary bile acid biosynthesis and bile secretion pathway in the MSTN+/− cattle. Targeted metabolomics data further showed that MSTN knockout significantly increased bile acid content in the liver, which may have resulted from enhanced bile acid synthesis due to the expression of bile acid synthesis genes, cholesterol 7 alpha-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1), and upregulation in the liver of the MSTN+/− cattle. These results indicate that MSTN knockout does not adversely affect bovine fitness but regulates bile acid metabolism via enhanced bile acid synthesis. This further suggests a role of MSTN in regulating metabolism.

Bile acid synthesis by human hepatoma cell line Hep-G2 is stimulated by low density lipoprotein

1988 ◽  
Vol 16 (4) ◽  
pp. 566-567
Author(s):  
HERMAN JAN KEMPEN ◽  
ELLEN LOMMERSE ◽  
RINA VAN SCHIE ◽  
ELLEN HEPP ◽  
PIET MEYER ◽  
...  
Keyword(s):  
Hepatoma Cell ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Hepatoma Cell Line ◽  
Low Density ◽  
Human Hepatoma ◽  
Hep G2 ◽  
Human Hepatoma Cell

The utilisation of esterified and unesterifled cholesterol derived from chylomicron remnants and high density lipoprotein for bile acid synthesis

1993 ◽  
Vol 21 (4) ◽  
pp. 459S-459S ◽  
Author(s):  
ELENA BRAVO ◽  
ALFREDO CANTAFORA ◽  
TAYFUN GULDUR ◽  
MALCOLM A. MINDHAM ◽  
PETER A. MAYES ◽  
...  
Keyword(s):  
Bile Acid ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
High Density ◽  
Chylomicron Remnants
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